A Multicenter, Open-Label, Single-Arm Study to Evaluate a Titration Regimen for Patiromer in Heart Failure Patients With Chronic Kidney Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 13
- 主要终点
- Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at the End of Treatment
研究概览
简要总结
The purpose of this study was to evaluate the feasibility of individualized titration of patiromer according to serum potassium. This study also assessed the safety and tolerability of patiromer and the effects of patiromer on serum potassium in heart failure (HF) participants with chronic kidney disease (CKD).
详细描述
This was an open-label, single-arm study to evaluate a titration regimen for patiromer in approximately 63 HF participants with CKD receiving one or more of the following: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), or beta blockers (BBs). This study was considered to be exploratory.
Upon successful completion of screening evaluations (-10 to -5 days prior to enrollment), all eligible participants were assigned at Baseline (Day 0 visit) to an initial dose of patiromer (20 g/day) and spironolactone (25 mg/day).
Study visits for enrolled participants were scheduled for Days 3, 7, 14, 21, 28, 35, 42, 49 and 56. A follow-up visit occurred on Day 63.
At selected study visits, patiromer or spironolactone doses may have been titrated. The study dosing algorithm was designed to maintain an individual's serum potassium value in the range of 4.0 - 5.1 mEq/L (based on local lab data).
Any participant with a local laboratory serum potassium value < 3.5 or > 5.5 mEq/L on two consecutive scheduled study visits, despite titration of patiromer or spironolactone, were withdrawn from the study, permanently discontinued patiromer and spironolactone, and returned for a follow-up visit within 7 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic HF clinically indicated to receive spironolactone therapy
- •Age 18 years or older
- •Local laboratory serum potassium values of 4.3 - 5.1 mEq/L at screening and baseline
- •CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2 at screening based on central lab creatinine measurement)
- •On at least one of the following HF therapies: ACEI, ARB, or BB
- •Females of child-bearing potential must be non-lactating, must have a negative serum pregnancy test at screening, and must have used a highly effective form of contraception for at least 3 months before study drug administration, during the study, and for one month after study completion
- •Male participants and/or their female partners of child-bearing potential must use a highly effective form of contraception during the study and for 3 months after study completion
- •Provide their written informed consent prior to participation in the study
排除标准
- •History of bowel obstruction, swallowing disorders, severe gastrointestinal disorders or major gastrointestinal surgery
- •Uncorrected primary severe valvular disease, known obstructive or restrictive cardiomyopathy, uncontrolled or hemodynamically unstable arrhythmia
- •Coronary-artery bypass graft, percutaneous intervention (e.g., cardiac, cerebrovascular, aortic), or major surgery including thoracic and cardiac, within 3 months prior to baseline or anticipated need during study participation
- •Heart transplant recipient, or anticipated need for transplant during study participation
- •Any of the following events having occurred within 2 months prior to baseline: unstable angina as judged by the Investigator, unresolved acute coronary syndrome, transient ischemic attack or stroke
- •Current dialysis participant, or anticipated need for dialysis during study participation
- •Prior kidney transplant, or anticipated need for transplant during study participation
- •Metastatic, late-stage or end-stage cancer with < 12 months life expectancy or at risk for tumor lysis syndrome
- •History of alcoholism or drug/chemical abuse within 1 year
- •Sustained systolic blood pressure > 180 or < 90 mmHg
- •Liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] > 3 times upper limit of normal
- •Loop and thiazide diuretics that have not been stable for at least 21 days prior to baseline or not anticipated to remain stable during study participation
- •Use of any intravenous cardiac medications within 21 days prior to baseline, or their anticipated need during study participation
- •Current use of polymer-based drugs (e.g., sevelamer, sodium polystyrene sulfonate, colesevelam, colestipol), phosphate binders (e.g., lanthanum carbonate), or other potassium binders, or their anticipated need during study participation
- •Use of potassium sparing medication including aldosterone antagonists or potassium supplements in the last 21 days prior to baseline
- •Use of any investigational medication within 30 days or 5 half-lives, whichever is longer, prior to baseline
- •Participants who have taken investigational product in this study, or a previous patiromer study
- •Inability to consume the study medication, or, in the opinion of the Investigator, inability to comply with the protocol
- •In the opinion of the Investigator, any medical condition, uncontrolled systemic disease, serious intercurrent illness, or extenuating circumstance occurring or persisting, within 30 days prior to baseline, that would significantly decrease study compliance or jeopardize the safety of the participant or affect the validity of the trial results
研究组 & 干预措施
patiromer
spironolactone + patiromer
干预措施: patiromer (Drug)
patiromer
spironolactone + patiromer
干预措施: spironolactone (Drug)
结局指标
主要结局
Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at the End of Treatment
时间窗: 56 days
次要结局
- Mean Number of Patiromer Titrations(56 Days)
- Percentage of Participants Requiring Patiromer Downtitration(56 Days)
- Percentage of Patients Whose Spironolactone Dose Was Increased Up to 50 mg/Day(56 Days)
- Mean Dose of Patiromer at End of Treatment(56 Days)
- Mean Patiromer Dose at Week 1(Up to Week 1)
- Percentage of Participants Discontinuing Due to Hyperkalemia (Serum Potassium > 5.5 mEq/L)(56 Days)
- Change in ACR From Baseline to Week 8 Among Participants With Urine ACR ≥ 30 mg/g at Baseline(Baseline and Day 56)
- Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 4(28 Days)
- Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 8(56 Days)
- Mean Change From Baseline in Serum Potassium to End of Treatment(56 Days)
- Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at Week 4(28 Days)
- Percentage of Participants With Serum Potassium in the Range of 4.0 - 5.1 mEq/L at the End of Treatment(56 Days)
- Mean Patiromer Dose at Week 4(Up to Week 4)
- Percentage of Participants Requiring Patiromer Uptitration(56 Days)
- Percentage of Participants With Serum Potassium in the Range of 3.5 - 5.5 mEq/L at Week 8(56 Days)
- Median Time to First Patiromer Dose Titration(56 Days)
- Mean Patiromer Dose at Week 8(Up to Week 8)
- Change in Urine Albumin to Creatinine Ratio (ACR) From Baseline to Week 4 Among Participants With ACR ≥ 30 mg/g at Baseline(Baseline and Day 28)